How vaccine-induced immune thrombotic thrombocytopenia (VITT) happens
Research will have both diagnostic and therapeutic implications

Date:
July 7, 2021
Source:
McMaster University
Summary:
Researchers recently discovered how, exactly, the COVID-19 vaccines
that use adenovirus vectors trigger a rare but sometimes fatal
blood clotting reaction called vaccine-induced immune thrombotic
thrombocytopenia, or VITT.



FULL STORY ==========================================================================
A McMaster University team of researchers recently discovered how,
exactly, the COVID-19 vaccines that use adenovirus vectors trigger a
rare but sometimes fatal blood clotting reaction called vaccine-induced
immune thrombotic thrombocytopenia or VITT.


==========================================================================
The findings will put scientists on the path of finding a way to better diagnose and treat VITT, possibly prevent it and potentially make
vaccines safer.

The researchers' article was fast-tracked for publication today by
the journal Nature in its accelerated article preview because of the
importance of the research.

"Our work also answers important questions about the connection between antibodies and clotting," said Ishac Nazy, principal investigator and corresponding author of the study. He added it will have both diagnostic
and therapeutic implications.

Nazy is the scientific director of the McMaster Platelet Immunology
Laboratory and an associate professor of medicine for the Michael
G. DeGroote School of Medicine at McMaster.

The COVID-19 vaccines using adenoviral vectors, such as those from
AstraZeneca and Johnson and Johnson, are associated with the VITT
clotting disorder caused by unusual antibodies to blood platelets that
are triggered by the vaccine.



==========================================================================
The study shows, at a molecular level, how those unusual antibodies stick
to components from blood platelets causing them to trigger clot formation.

"The antibodies stick to the platelet protein called platelet factor
4 (PF4) in a very unique and specific orientation, which allows them
to align with other antibodies and platelets in the precise formation
that leads to a self- perpetuating vicious cycle of clotting events,"
said Nazy.

"These disease-causing aggregates quickly activate platelets, creating
a highly intense clotting environment in patients," he added.

The dangerous reaction to the adenovirus vector vaccines has been found
to occur in one in 60,000 of people receiving the vaccine in Canada.

"The intention of our study was to better understand how the severe
clots which characterize VITT develop," said Donald Arnold, study co-investigator and co- medical director of the McMaster Platelet
Immunology Laboratory.



==========================================================================
"A basic principle of medical care is to understand how the disorder
happens and, in doing so, develop better treatments." John Kelton, co-investigator of the study and co-medical director of the McMaster
Platelet Immunology Laboratory, added: "We believe that this study is
important because it clarifies how the clotting ensues, and because we
have been able to identify the molecules involved.

"The next step is to develop a rapid diagnostic and accurate test to
diagnose VITT. Our major interest is now to move upstream from how the
clots happen to preventing them from occurring." Current rapid tests
yield false-negative results, and testing relies on more time-consuming
tests to confirm VITT. This study now explains why the rapid tests
frequently fail and allows for new strategies to improve diagnostic
testing.

The investigators altered the molecular composition of the PF4 protein
and, using this technology, were able to identify the binding region on
the protein.

The research team included Angela Huynh, a research scientist in the
McMaster Platelet Immunology Laboratory, and Mercy Daka, a graduate
student of McMaster's Department of Biochemistry and Biomedical Sciences.

The researchers thanked the agencies supporting the research, including
the Public Health Agency of Canada, the Canadian Institutes of Health
Research (CIHR), and the Ontario Ministry of Health.

========================================================================== Story Source: Materials provided by McMaster_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Angela Huynh, John G Kelton, Donald M Arnold, Mercy Daka,
Ishac Nazy.

Antibody epitopes in vaccine-induced immune thrombotic
thrombocytopenia.

Nature, 2021; DOI: 10.1038/s41586-021-03744-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210707112432.htm

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